53 articles - From Saturday Apr 02 2022 to Friday Apr 08 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Leukemia |
Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Evidence-based recommendations for prevention and management of infectious complications and specific alerts regarding the potential for drug-drug interactions were developed and discussed in a plenary session with the panel of experts until consensus was reached. The set of recommendations was posted on the ECIL website for a month for comments from members of EBMT, EORTC, ICHS and ELN before final approval by the panelists. While a majority of these agents are not associated with a significantly increased risk when used as monotherapy, caution is required with combination therapy such as venetoclax plus hypomethylating agents, gemtuzumab ozogamicin plus cytotoxic drugs or midostaurin added to conventional AML chemotherapy. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Monoclonal Gammopathy of Renal Significance (MGRS): Real-World data on outcomes and prognostic factors. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS. |
Prediction of Survival with Intensive Chemotherapy in Acute Myeloid Leukemia. The new proposed predictive model for survival with intensive chemotherapy in patients with AML is robust and can be used to advise patients regarding their prognosis, to modify therapy in remission (e. g. proposing allogeneic stem cell transplantation in first remission), and to compare outcome and benefits on future investigational therapies. |
| Blood |
ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia. Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared to antibody-positive (functional assay-negative) controls than to antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal SNP. Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia. |
| Blood Adv |
Cytokine pathway variants modulate platelet production: IFNA16 is a thrombocytosis susceptibility locus in humans. ET sub-stratification analysis by variant IFNA16 demonstrated statistically significant increase in interferon-a16 levels (p = 0.002) among 16 quantifiable cytokines. Recombinantly-expressed variant IFN-a16 encompassing 3 linked non-synonymous SNVs (E65 H95 P133) retained comparable antiviral (AV) and pSTAT signaling profiles as native IFN-a16 (V65 D95 A133) or IFN-a2, although both native and variant IFN-a16 demonstrated stage-restricted differences (compared to IFN-a2) of interferon-regulated genes in CD34+-stimulated megakaryocytes. These data implicate IFNA16 (IFN-a16 gene product) as a putative susceptibility locus (driver) within the broader disrupted cytokine network evident in MPNs, and provide a framework for dissecting functional interactive networks regulating stress or MPN thrombopoiesis. |
Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation. However, IDH1 R132 and IDH2 R172 MRD positivity in remission at HSCT associated with an increased risk of relapse, while IDH2 R140 mutations did not. The IDH2 R140 variant allele frequency (VAF) at diagnosis was higher - clustering around 50% - and the mutation clearance at HSCT in morphologic remission was much lower compared to IDH1 R132 and IDH2 R172. In our cohort, IDH2 R140 mutations behaved more like a clonal hematopoiesis related abberation, while IDH1 R132 and IDH2 R172 habored AML disease specific features. |
Incidence and clinical impact of bleeding events in older patients with acute venous thromboembolism. After adjustment, active cancer (sub-hazard ratio [SHR] 1.81, 95%CI 1.12-2.93) and low physical activity (SHR 1.88, 95%CI 1.19-2.98) were associated with MB, and high risk of falls with CRNMB (SHR 2.04, 95%CI 1.39-3.00). Older patients anticoagulated for VTE had a high incidence of MB and CRNMB, and these bleeding episodes caused a great burden of disease. Physicians should carefully weigh the risks/benefits of extended anticoagulation in the older population with VTE. |
Longitudinal study of 2 patients with cyclic thrombocytopenia, STAT3, and MPL mutations. In addition, both patients had clonal T-cell populations that remained stable throughout platelet count cycles. These mutations and clonal T cells may potentially involve in the pathogenic baseline in these patients rendering exaggerated persistent thrombopoiesis oscillations of their intrinsic rhythm upon homeostatic perturbations. This work provides new insights into the pathophysiology of CTP and possible therapies. |
Molecular subclusters of follicular lymphoma: a report from the UK's Haematological Malignancy Research Network. Poorer OS in the aSHM group (p=0.04) was associated with older age, however overall tumor genetics provided limited information to predict individual patient risk. Our approach identifies three molecular subclusters of FL linked to differences in underlying mechanistic pathways. These clusters, which may be further resolved by the inclusion of translocation status and wider mutation profiles, have implications for understanding pathogenesis as well as improving treatment strategies in the future. |
Up to 8 Years Follow-up From RESONATE-2: First-Line Ibrutinib Treatment for Patients With Chronic Lymphocytic Leukemia. With up to 8 years of follow-up, 42% of patients remain on single-agent ibrutinib. Long-term RESONATE-2 data demonstrate sustained benefit with first-line ibrutinib treatment for CLL, including for patients with high-risk genomic features. These trials are registered at as NCT01722487 and NCT01724346. |
| Blood Cancer J |
Examining allostatic load, neighborhood socioeconomic status, symptom burden and mortality in multiple myeloma patients. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM. |
Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma. Using our pDC-MM coculture models, we found that blockade of CD73 with anti-CD73 Abs: decreases adenosine levels; activates MM patient pDCs; triggers cytotoxic T lymphocytes (CTL) activity against autologous patient MM cells. Combination of anti-CD73 Abs and an immune-stimulating agent TLR-7 agonist enhances autologous MM-specific CD8 + CTL activity. Taken together, our preclinical data suggest that the therapeutic targeting of CD73, alone or in combination with TLR-7 agonist, represents a promising novel strategy to restore host anti-MM immunity. |
Ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory myeloma: MUKeight phase II randomised controlled trial results. Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial. |
| Haematologica |
Iron- and erythropoietin-resistant anemia in a spontaneous breast cancer mouse model. Instead, an early shift in the commitment of common myeloid progenitors from the erythroid to the myeloid lineage resulted in increased myelopoiesis and in the excessive production of neutrophils that accumulate in necrotic tumor regions. This process could neither be prevented by iron nor erythropoietin (EPO) treatment. Trp53floxWapCre mice are the first mouse model where EPO-resistant anemia is described and may serve as a disease model to test therapeutic approaches for a subpopulation of human cancer patients with normal or corrected iron levels that do not respond to EPO. |
The deglycosylated form of 1E12 inhibits platelet activation and prothrombotic effects induced by VITT antibodies. This strongly supports that 1E12 and VITT antibodies recognize overlapping epitopes on PF4. In conclusion, 1E12 is a potentially important tool to study the pathophysiology of VITT, and for establishing mouse models. On the other hand, DG-1E12 may help the development of a new drug that specifically neutralizes the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT. |
Treatment-free remission in chronic myeloid leukemia patients treated front-line with nilotinib: 10-year follow-up of the GIMEMA CML 0307 study. The overall TFR rate, calculated on al enrolled patients, was 24.7% (18/73 patients). Seventeen patients (23.3%), at a median age of 69 years, had at least one arterial obstructive event. In conclusion, the use of NIL front-line in CP-CML can induce a stable TFR in a relevant number of patients, although cardiovascular toxicity remains of concern. |
| Lancet Haematol |
Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. In patients with diffuse large B-cell lymphoma who had previous CAR T-cell therapy and received doses of 80 mg or higher, the objective response rate was 33% (ten of 30) and complete response rate was 27% (eight of 30). Interpretation Odronextamab monotherapy showed a manageable safety profile and encouraging preliminary activity, including durable responses in heavily pretreated patients with B-cell non-Hodgkin lymphoma, supporting further clinical investigation in phase 2 and 3 trials. Funding Regeneron Pharmaceuticals. |
| Leukemia |
Cyclin-dependent kinase inhibitor fadraciclib (CYC065) depletes anti-apoptotic protein and synergizes with venetoclax in primary chronic lymphocytic leukemia cells. While fadraciclib, venetoclax, and the combination each had distinct kinetics of cell death induction, their activities were reversible, as no additional cell death was induced upon removal of the drugs. The best combination effects were achieved when both drugs were maintained together. Altogether, this study provides a rationale for the clinical development of fadraciclib in CLL, either alone or in combination with a Bcl-2 antagonist. |
Identification of a c-MYB-directed therapeutic for acute myeloid leukemia. Although WFA has been reported to have pleiotropic anti-cancer effects, we demonstrate that its anti-AML activity depends on c-MYB modulation and can be partially reversed by a stabilized c-MYB mutant. c-MYB ablation results from disrupted HSP/HSC70 chaperone protein homeostasis in leukemia cells following induction of proteotoxicity and the unfolded protein response by WFA. The widespread use of WFA in traditional medicines throughout the world indicates that it represents a promising candidate for repurposing into AML therapy. |
Phase 2 study of oral thalidomide-cyclophosphamide-dexamethasone for recurrent/refractory adult Langerhans cell histiocytosis. Patients with risk organ involvement had similar EFS compared to patients without risk organ involvement (P |
| Thromb Haemost |
Do antiangiogenics promote clot instability? Data from the TESEO prospective registry and Caravaggio clinical trial. Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success. However, treatment interruption is a safe procedure only with appropriate patient selection and monitoring. Clinical and biological factors associated with better outcomes do not yet offer a precise stratification of patients according to their risk of relapse. This article aims at reviewing the leading studies present in the field in order to define eligibility criteria for discontinuation and predictors of success. |
| Ann Oncol |
| Blood |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
A new risk-assessment tool for venous thromboembolism in advanced lung cancer: a prospective, observational study. The items extracted in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 |
Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment. |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |